Immunomodulatory Effects of IL-12 on Allergic Lung Inflammation Depend on Timing of Doses

Sanjiv Sur, Johnsimon Lam, Page Bouchard, Anastasia Sigounas, Donald Holbert, W. James Metzger

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-γ expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-γ, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-γ expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.

Original languageEnglish (US)
Pages (from-to)4173-4180
Number of pages8
JournalJournal of Immunology
Volume157
Issue number9
StatePublished - Nov 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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